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Adnexal Mass: Diagnosis and Management

Learn about adnexal masses, their potential for malignancy, and the importance of accurate diagnosis and appropriate management. Discover the impact of surgical interventions and the role of gynecologic oncologists in improving survival rates for ovarian cancer.

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Adnexal Mass: Diagnosis and Management

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  1. به نام خداوند بخشنده و مهربان

  2. Adnexal MassObservation vs Intervention M.Mohit Gynecologist Oncologist NAIGO, Bahman 1395

  3. Ovarian Cancer Ovarian Cancer is a Major Women's Health Problem 7th most common cancer in women in US: 3% of all female malignancies About 1/3 of invasive female genital organ cancers Deadly disease with High morbidity and mortality 4th cause of women cancer mortality (6%) : 1/ 44 min Leading cause of death of gyn malignancies: 53% death of gyncancers

  4. Epidemiology of ovarian cancer • Highest fatality/case ratio of all the gynecologic malignancies • fatality /case: - Ovarian ca: 15520 /21650 ≈80/100 - Cervical ca: 3710 /10500 ≈ 37/100 - Endometrial cancer: 7310 /40800 ≈ 16/100

  5. Epidemiology of ovarian cancer - Age Peak incidence: 56-60 y/o, rises from 20-80 ,then decline Ovarian mass: Age < 40 : 1/10 invasive or borderline Age > 40 : 1/3invasive or borderline - Postmenopause: 30% of neoplasms are malignant - Premenopause: 7% of epithelial neoplasms are malignant Epithelial cancers: the most common ovarian cancer Ovarian ca before age 20: 1% epithelial, 2/3 germ cell

  6. Ovarian Cancer Greatest clinical challenge in all gynecologic cancers Usually asymptomatic until advanced disease: >2/3 at diagnosis Major surgical challenge, requires intensive & often complex therapies, extreme demand in pt's psychological & physical energy Appropriate diagnosis & optimal treatment can improves survival: - Early stage diagnosis - Optimal surgery ( gyn oncologist, High volume surgeons & centers) - Suitable chemotherapy

  7. Survival Rates for Ovarian Cancer Need to be Improved Heintz APM, et al. FIGO Annual Report on the Results of Treatment in Gynecologic Cancers. 2000; 24 :107-138. Holschneider CH, Berek JS. Semin Surg Oncol. 2000;19:3-10.

  8. Surgery can Impact Survival • Surgery by gynecologic oncologist:12 month survival advantage • Complete surgical staging / Cytoreductive surgery • Complete surgical staging: to Define extent of disease, Determine the need for adjuvant treatment, Provide prognosis, Outline a plan of care • Optimal surgical debulking: remove all tumor in advanced tumor by Hysterectomy, removal of ovaries, omentectomy, bowel resection if needed, peritoneal stripping, diaphragmatic stripping, l.n. debulking, …

  9. Oncology Specialist Most Likely toPerform Comprehensive Surgery * South Carolina admissions Goff BA et al. Cancer. 2007;109(10):2031-2042.

  10. High Volume Surgeons Most Likely to Perform Comprehensive Surgery Goff BA et al. Cancer. 2007;109(10):2031-2042.

  11. Less than Half of US Ovarian Cancer Surgery is at High Volume Hospital Goff BA et al. Cancer. 2007;109(10):2031-2042.

  12. Significantly Higher Survival Rates with Oncology Specialists Type of Surgeon Impacts Survival Rates Type of Hospital Impacts Survival Rates TH: Teaching hospital NTH: Nonteaching hospital Paulsen T et al. Int J Gynecol Cancer. 2006;16(Suppl 1):11-17.

  13. Adnexal mass • Frequently found in both symptomatic and asymptomatic women • Frequency: 7.8% in reproductive age, 2.5-18% in postmenopausal • Usually detected by gynecologist, most incidentally in pelvic exam or imaging and less commonly present with acute or intermittent pain • Can have gynecologic or non-gynecologic etiologies • Gynecologic:ovarian(benign or malignant), tubal(hydrosalpynx, EP, …), paratubal, uterine( leiomyoma, anomalies, hemato or pyometra,…) • Non-Gynecologic: GI, urologic, metastatic, retroperitoneal tumors ( LAP, sarcoma, neurologic tumors),…

  14. Adnexal mass • The discrimination between benign and malignant adnexal masses is central to clinical management and surgical planning in adnexal mass • Characterizing ovarian pathology is fundamental to optimizing management in both pre- and post-menopausal women: - Inappropriate referral to oncology services - Unnecessary surgery - Overly radical interventions compromising fertility in young women • For adnexal masses highly suspicious for cancer, women should be referred a gynecologic oncologist and facility for optimal care. • Failing to recognize cancer significantly impact on prognosis

  15. Adnexal mass • Main purpose of the diagnostic evaluation of adnexal tumors is to exclude the possibility of malignancy • Prediction of malignancy of an ovarian mass is critical for: • Management ( surgery vs observation) • Choice of surgeon • Center and • Surgical technique • Accurate preoperative evaluations are pivotal for optimal managemen

  16. Evaluation of adnexal mass:How to predict the risk of malignancy in adnexal mass?

  17. Goal of our diagnostic evaluations on a pelvic mass? prediction of it’s behavior/exclude malignancy • How we can exclude malignancy? • Is there any tool for definite diagnosis?

  18. - «در شناختن حق بیشتر خلاف در میان خلق چنین است که همه از وجهی راست گفته باشند و لکن بعضی را ببینند، پندارند که همه را بدیدند ومثال ایشان چون گروهی نابینا باشد که.....» کیمیای سعادت امام محمد غزالی پیل اندر خانه ای تاریک بود... در کف هر یک اگر شمعی بدی اختلاف از گفتشان بیرون شدی چشم حس همچون کف دست است و بس نیست کف را بر همه او دسترس

  19. Evaluation of pelvic masses • Clinical evaluation of patient (patient’s characteristics, risk factors, history and physical examination), imaging results and serum markers help us to separate masses into the categories of “probably benign”, “uncertain” and “likely malignant” which can guide appropriate management.

  20. Tools for Assessing Risk of Ovarian Cancer in a Mass Tools as malignancy marker: • Clinical: - History: age , menopausal status, family history, Wt loss,.. - P/E : firm nodular adherent pelvic mass, evidences of advanced tumor • Paraclinical: - Imaging (Sono, CT and MRI): bilaterality, solid part, large tumor size( >10cm), mural nodules and vegetation, thick wall and septation, detection of omental or peritoneal nodularity and seeding, ascites, lymphadenopathy - Serum tumor markers: CA125, … • Combinations of markers

  21. Clinical evaluation Risk factors: • Age: most important independent risk factor of ovarian cancer, about 70% > 55y/o • Menopausal status: risk of malignancy is much greater than premenopausal • Familial history of breast or ovarian cancer: most important personal risk factor of ovarian cancer. Different from familial ovarian cancer syndrome - lifetime probability of general population: 1.6% - one affected family member: 5% - woman with BRCA1 mutation: 41-46% by age 70 - woman with BRCA1 mutation: 10-27% by age 70 - woman with Lynch syndrome: 5-10% by age 70 ACOG Practice Bulletin No 174, Nov 2016

  22. Clinical evaluation • Detailed history and Symptoms: • Patient may present history and symptoms that can refine the differential diagnosis: genetic/familial high risk assessment, potential of pregnancy, acute onset pain, intermittent acute pain, fever, chills, vaginal discharge, secondary dysmenorrhea, dyspareunia, chronic pelvic pain, AUB, bloating, early satiety, wt loss,… • Physical examination: irregular, firm, nodular, bilateral mass or associated with ascites are concerning for malignancy ACOG Practice Bulletin No 174, Nov 2016

  23. Imaging of mass • Ultrasonography: - TVS: most commonly used for evaluation of adnexal mass - TAS: distorted pelvic structures, mass extended beyond the pelvis or when TVS cannot be performed • Color Doppler ultrasonography • CT, MRI, PET: not recommended for initial evaluation of adnexal mass

  24. TVS • Transvaginal ultrasound has long been considered the imaging modality of choice for the evaluation of adnexal masses: • Available, high quality images, detailed descriptions of macroscopic appearance of mass, and least expensive of all imaging modalities currently available • Advantage: widespread availability, good pt tolerability, cost effectiveness • Main limitation for distinguishing benign from malignant mass: low specificity, low PPV especially in premenopausal women

  25. Gray scale TVS • Recommended modality for suspected adnexal mass • No alternative imaging modality has sufficient superiority to TVS to justify its routine use • High frequency gray scale TVS: high resolution images of mass that approximate it’s gross anatomic appearance • Image quality is operator dependent • High inter-observer agreement among experts • In premenopause: expert sonography reached the highest discriminative power with PPV of 0.45, and an NPV of 0.99.

  26. MR Imaging • MRI: limited data • May have superior ability compared to TVS in correctly classifying malignant masses at the expense of lower detection rate. Help clarify malignant potential in patients in whom ultrasonography may be unreliable, MRI is the most appropriate test • Often helpful in differentiating the origin of pelvic masses that are not of ovarian origin, specially leiomyoma

  27. CT • CT: best use of CT is not to detect or characterize pelvic masses but to evaluate: • In cases in which extra-ovarian disease and abdominal metastasis suspected or needs to be ruled out, CT is the most useful technique • To evaluate an alternate primary cancer site when cancer is suspected based on sono, P/E or serum markers

  28. Doppler technology • Doppler technology: Evaluation of an adnexal mass by Doppler technology alone is not recommended. Doppler technology should be combined with a morphology assessment • Increase the specificity of two dimensional gray scale sonography • Overlapping range of values of resistive index, pulsatility scale, max systolic velocity between benign and malignant masses • In attempt to overcome this overlap: Three dimensional ultrasound of vasculature of mass, better discrimination than Doppler sono

  29. What ultrasound finding suggest malignancy? • Findings should raise concern regarding malignancy are: - Size: greater than 10 cm - Papillary or solid component - Irregularity - Ascites - High color Doppler flow • Many research on different various ultrasonographic scoring systems to quantify cancer risk based on morphology • Generally all evaluated scoring systems were found to have an acceptable level of sensitivity and specificity

  30. What ultrasound finding suggest benign disease? • Characteristics of benign masses: simple appearance with - Thin smooth walls - Absence of septation, solid component • Absence of internal blood flow in Doppler • Highly likely (almost always) to be benign in any age group regardless of menopausal status and often regress • Malignancy rate in most series: 0-1%

  31. Cutoff size of need for surgery of simple masses • Cutoff size of need for surgery of simple masses:?? • Often ≥ 10 cm • Large prospective study: 2763 postmenopause cystic < 10 cm 2/3 regress, no case of malignancy in 6.3 y mean f.u.ObstetGynecol 2003;102:594. • In 1148 unilocularcyst: 11, 0.96% were malignant (7/11 , sono did not detect macroscopic papillary projection or solid part seen at surgery) Ultrasound ObstetGynecol 2013;41:80. ACOG Practice Bulletin No 174, Nov 2016

  32. Ultrasound finding suggest selected benign masses • Some ultrasound findings may be specific for selected benign masses (level II evidences, small descriptive studies): • Endometrioma: specificity 89%, sensitivity 83%, PPV 77%, NPV 92% • Mature Teratoma: 98% accuracy in 155 case of dermoidspecificity 99%, sensitivity 58% • Hydrosalpinx: specificity 99%, sensitivity 93%,

  33. Ultrasonography-based morphology scoring systems • Generally various models all are able to distinguish benign from malignant masses in most instances • 2014 systematic review and meta-analysis compared various morphologic (ultrasound scoring) malignancy prediction models. Hum Reprod Update 2014;20:449-62 • Best performing models were: • IOTA group logistic regression model 2(LR2): patient age + 5 sonofindings: sensitivity 92% , specificity 83% • IOTA simple rules model: including 10 ultrasound findings: sensitivity 93% , specificity 81% ACOG Practice Bulletin No 174, Nov 2016

  34. Ultrasound based prediction model (LR2) developed by the International Ovarian Tumor Analysis (IOTA) study offers better diagnostic performance than CA125 alone.

  35. Laboratory Testing • To evaluate likelihood of malignancy and need for surgery of a mass • CBC, pregnancy test, STD, U/A, stool-OB,... • Serum markers: CA125, HE4, markers of less common ovarian histopathology: BhCG, LDH, AFP, Inhibin,… • CA125: • Specificity and PPV are consistently higher in postmenopausal • Cutoff :Premenopause: 30 U/ml Postmenopause & hysterectomy: suggested 20 -26 U/ml - Epithelial ovarian cancer: - 83% CA125 ≥ 35 IU/ml - ↑ 50% in stage I - ↑ 90% in more advanced stages

  36. CA125 • Best known ovarian cancer serum tumor marker • Biomarker in epithelial ovarian cancer • Overall sensitivity in distinguishing malig: 61-90%, spec 71-93% • PPV: 35-91, NPV 67-90%. wide variation • Elevated only in ½ early stage, rarely elevated in germ cell, stromal and mucinous • Positive in many non malignant conditions: myoma, PID, ascites of any etiology, endometriosis, IBD, SLE,…

  37. CA125 • Limitations : • - Low specificity/ PPV in premenopausal years: Elevated levels in • benign gynecological diseases • - Low sensitivity/NPV: in Stage I ovarian cancer 50%. • CA 125 alone is not a sensitive marker for screening of pelvic mass • - Elevated level in some other cancers • - In premenopausal: Using > 35 U/mL as threshold 78% sensitivity • and 78% specificity

  38. CA125 • In premenopause women: • less value in prediction, extreme values increase suspicious and concern for malignancy, even though benign conditions such as endometrioma can have CA125 of 1000 or greater • Threshold: ?, no evidence based threshold is currently available • Prior ACOG guidance used ≥ 200 for referral of premenopause • Gynecologist should integrate CA125 with other factors in judging the need for referral

  39. ACOG 2007 simple Guidelines for referral of ovarian mass to GYN- Oncologist ACOG Practice Bulletin. Obstet Gynecol. 2007;110:201-213. • Premenopausal - CA125 > 200 - Ascites - Evidence of metastasis • Family history of breast or ovarian cancer • Postmenopausal - CA125 >35 - Ascites - Fixed or nodular mass - Evidence of metastasis • Family history of breast or ovarian cancer

  40. CA125 • In postmenopause: • Both sensitivity and specificity of elevated CA125 for cancer diagnosis in setting of pelvic mass is higher after menopause • Elevated CA125 + pelvic mass in post menopause: highly suspicious to malignancy & should be referred to Gyn Oncologist • In post menopause: ↑ CA125 without ovarian ca is a risk factor of death from other malignancies • Combinations of expert sonography with CA-125 serum measurement in postmenopause achieved the highest discriminative power: • Combination of CA-125 & expert sono: PPV 0.89 and NPV of 0.97

  41. Dual Marker: CA125+ HE4 • 1997: Maggino et al. examined sens and spec of CA125 at various cutoffs • At cutoff of 35: sensitivity of 78.3% , specificity 82% • Increasing cutoff to 65: sensitivity decreased to 71.7% and specificity increased to 92.5% • 20%of EOC express little, if any, CA125 • In early stage ↑ to 50% • So: not sufficient as single marker

  42. Dual marker: CA125+HE4 • 2007: Moore et al. examined a panel of biomarkers. • Dual marker of HE4 + CA125: highest sensitivity of various combinations, increased sensitivity of CA125 alone • HE4 is elevated in > 50% of tumors that do not express CA125 • Addition of HE4 to CA125 enables higher detection of malignancies in: 1- Patients with tumor that do not express CA125 and will be missed by algorithm CA125 alone 2- Early stage disease compared with CA125 • So it’s addition to CA125: ↑ sensitivity

  43. Panels of Serum Tumor Markers • Panels of biomarkers: • FDA approved two panel for assessment of risk of malignancy in adult women (>18) with pelvic mass that require surgery: • MIA: Multivariate Index Assay (OVA1™:CA125 II+ transferrin+ transthyrenin+ apolipoprotein A1+ B2 microglobulin) • ROMA: Risk Of Ovarian Malignancy Algorithm(CA125 + HE4+ menopausal status) ACOG Practice Bulletin No 174, Nov 2016

  44. Role of Serum biomarker panel testing • Alternative to CA125 alone in determining the need for referral or gyn oncology consult when a mass need surgery • Note: not recommended for use in initial evaluation of mass • CA125 alone: 65.7% predict ovarian malignancy in early stage

  45. MIA • Multivariate index assay: - Correctly predict in 91.4% • Abnlin 83.3% of malignancies which clinical impression was benign • Abnl in 70.8% of malignancies with normal CA125 • Sens: 95.3%. more than clinical impression and CA125 • Add radiologic finding to MIA: ↑ Sensto 98% ( for TVS) and 97%(for CT) ↑ NPV to 99% ( for TVS) and 94%(for CT) Note: Low risk imaging + low risk MIA: < 1-2% false negative

  46. ROMA • Risk of malignancy algorithm (ROMA): • More sensitive and specific than CA125 alone • In cohort of 531 women with epithelial ovarian cancer 93.8% of diagnosed as high risk before surgery • Pre-menopause: sens 92.3% , spec 75% • Post-menopause: sens 76.5%, spec 74.8% • ROMA compared with MIA, Prospective analysis of 146 cases of malignancy: • MIA was more sensitive than ROMA (97% VS 87%) • ROMA was more specific than MIA (83% VS 55%) • NPV of both tests were similar(98 vs 96%) ultrasound ObstetGynecol 2013;42:218.

  47. Combination of different markers Sonography + CA125: In postmenopausalwith adnexal mass seems to improve sensitivity and specificity of predicting adnexal malignancies. In contrast In premenopausal women the consideration of CA-125 levels with Doppler sonomight confuse differential of ovarian masses As a standalone modality, serum cancer antigen 125 is not recommended for distinguishing between benign and malignant adnexal masses

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